Clinical readiness of Uzap - the minimally invasive Overactive Bladder treatment

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Abstract Overactive bladder (OAB) severely impacts over 12% of the adult population in the United States – roughly 30 million people (Irwin, et al., 2006). Pressing and frequent urges to urinate, arousal from sleep, and sometimes incontinence, result in immense psychosocial and financial costs, leading to an estimated annual economic burden of >$70B in the US alone (Reynolds, et al., 2016). Current OAB interventions are varied and include pharmaceuticals, neurostimulators, botulinum toxin injections, and surgical approaches, all of which have adverse side effects and lack widespread and enduring efficacy. In addition, drug therapies require long-term dosing and other treatments can require repeat clinical interventions. Stellartech Research Corporation is developing the NewUro Uzap device for transurethral radiofrequency mucosal partitioning. It is the only minimally-invasive, single-session, non-drug, non-implant therapy for alleviating the symptoms of OAB without compromising voiding function. Research has shown excessive electrical connectivity within the bladder mucosa in models of overactivity (Kanai et al., 2007). This results in exaggerated propagation of wave-like intrinsic electrical and mechanical activity, which is anticipated to be amenable to therapy by minimally invasive thermal ablation of mucosal isolation lines by the Uzap. The innovations behind the Uzap system are already covered by 7 granted patents. Preliminary studies of Uzap ablation on whole pig bladder and tissue specimens demonstrated reduced contractile response to agonists. Successful preclinical safety and performance tests were completed in ex vivo and preliminary in vivo porcine models. This Fast-Track proposal seeks, in Phase 1, to demonstrate long-term in vivo safety and durability of Uzap therapy, and, in Phase 2, to 1) perform a long-term animal safety and efficacy study; 2) optimize system and electrode design and usability and fabricate Verification and Validation units; 3) perform Verification and Validation tests; hold a pre-IDE (Investigational Device Exemption) meeting and submit an IDE application for a future First-In- Human trial of 30 female patients with refractory overactive bladder with incontinence. The rigorous work proposed will create a firm base for advancing the Uzap to the clinical phase and towards commercialization, in order to provide relief for millions of patients and eliminate the need for implants or repetitive clinical interventions.